Hematopoietins, i.e., hematopoietic growth factors, are proteins that promote the survival, growth and differentiation of hematopoietic cells. Colony stimulating factors (CSFs) are a subset of these hematopoietic growth factors tht are characterized by the ability to support the growth, in vitro, of colonies of hematopoietic cells arising from progenitor cells of bone marrow, fetal liver and other hematopoietic organs.
The biochemical and biological identification and characterization of certain hematopoietins has been hampered by the small quantities of the naturally occurring factors available from natural sources, e.g., blood and urine. With recombinant genetic engineering techniques, however, some of these hematopoietins have been molecularly cloned, heterologously expressed and purified to homogeneity. [See D. Metcalf, "The Molecular Biology and Functions of the Granulocyte-Macrophage Colony Stimulating Factors," Blood, 67(2):257-267 (1986).] Among these hematopoietins are human and murine GM-CSF, human G-CSF, human CSF-1 and murine IL3. Human IL-3 has also recently been identified [Y. C. Yang et al., Cell, 47(1):3-10 (1986)]. Both human GM-CSF [See, R. Donahue et al., Nature, 321:872-875 (1986)] and murine I L3 [See J. Kindler et al, Proc. Natl. Acad. Sci. U.S.A., 83:1001-1005 (1986)] have a demonstrated effect on hematopoiesis in vivo.
A cDNA sequence for human urinary CSF-1 has been reported by E. S. Kawasaki, et al., Science, 230:291-196 (1985) [hereinafter "Kawasaki"], which, when expressed in a COS cell transient expression system, produced a 26 kD protein that competed with labeled murine CSF-1 in a radioreceptor assay. The protein also reportedly stimulated mouse bone marrow proliferation, resulting in predominantly monocytic lineage type colonies in the mouse bone marrow assay. The protein biological activity was reportedly inhibited by neutralizing antisera for CSF-1.